Data Collection Study of Patients with Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT with RIC

Recruiting

• Conditions: Primary Immunodeficiency (PID); Inherited Metabolic Disorders (IMD); Inflammatory Conditions; Congenital Bone Marrow Failure Syndromes; Hereditary Anemias

• Registration Number: NCT04528355
• Lead Sponsor: Paul Szabolcs

Brief Summary

This is a data collection study that will examine the general diagnostic and treatment data associated with the reduced-intensity chemotherapy-based regimen paired with simple alemtuzumab dosing strata designed to prevented graft failure and to aid in immune reconstitution following hematopoietic stem cell transplantation.

Detailed Description

Hematopoietic stem cell transplantation (HSCT) from a healthy donor can cure or alleviate a broad spectrum of non-malignant disorders (NMD). Although reduced-intensity conditioning (RIC) regimens promise decreased treatment-related morbidity and mortality, graft failure and infections are limiting the use of RIC in chemotherapy-naive patients. Dr. Szabolcs have completed several trials to evaluate a novel RIC regimen of alemtuzumab, hydroxyurea, fludarabine, melphalan, and thiotepa. The last trial at UPMC Children's Hospital of Pittsburgh of a highly effective and biologically rational chemotherapy-based RIC regimen paired with simple alemtuzumab dosing strata was tested and resulted in outstanding survival and remarkably low rates of graft failure. The favorable outcome described may serve as a toxicity and efficacy reference for emerging gene therapy strategies as well.

This prospective collection of clinical data will allow the investigators to further assess engraftment, GVHD, immunosuppressant use and overall survival in this patient population.

Study Timeline

• Study First Submitted: 2020-08-18
• Study Start: 2020-08-20
• Study First Submitted QC: 2020-08-25
• Study First Posted: 2020-08-27
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-07
• Last Update Posted: 2025-01-09
• Primary Completion: 2025-12-31
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Patient, parent, or legal guardian must have given written informed consent.

2. Patient must be 2 months to 60 years (inclusive) of age at time of consent for all diagnoses.

3. Patients should have a non-malignant disorder amenable to treatment by stem cell transplantation, including but not limited to the following:

   A. Primary Immunodeficiency Syndromes

   • Severe Combined Immune Deficiency (SCID) with NK cell activity
   • Omenn Syndrome
   • Bare Lymphocyte Syndrome (BLS)
   • Combined Immune Deficiency (CID) syndromes
   • Combined Variable Immune Deficiency (CVID) syndrome
   • Wiskott-Aldrich Syndrome
   • Leukocyte adhesion deficiency
   • Chronic granulomatous disease (CGD)
   • Hyper IgM (XHIM) syndrome
   • IPEX syndrome
   • Chediak-Higashi Syndrome
   • Autoimmune Lymphoproliferative Syndrome (ALPS)
   • Hemophagocytic Lymphohistiocytosis (HLH) syndromes
   • Lymphocyte Signaling defects

   B. Congenital Bone Marrow Failure Syndromes

   • Congenital Amegakaryocytic Thrombocytopenia (CAMT)
   • Osteopetrosis

   C. Inherited Metabolic Disorders (IMD)

   • Mucopolysaccharidoses

     • Hurler syndrome (MPS I)
     • Hunter syndrome (MPS II)

   • Leukodystrophies

     • Krabbe Disease, also known as globoid cell leukodystrophy
     • Metachromatic leukodystrophy (MLD)
     • X-linked adrenoleukodystrophy (ALD)

   • Other inherited metabolic disorders

     • Alpha Mannosidosis
     • Gaucher Disease
     • Other inheritable metabolic diseases where HSCT may be beneficial

   D. Hereditary Anemias

   • Thalassemia major
   • Sickle cell disease (SCD)
   • Diamond Blackfan Anemia (DBA)

   E. Inflammatory Conditions

   • Crohn's Disease or Inflammatory Bowel Disease
   • IPEX or IPEX-like Syndromes
   • Rheumatoid Arthritis
   • Other inflammatory conditions where HSCT may be beneficial

4. Subjects receive either umbilical cord blood, bone marrow, or peripheral blood stem cell transplant with an alemtuzumab, melphalan, thiotepa, fludarabine and hydroxyurea-based, reduced-intensity conditioning regimen, according to clinical practice at UPMC Children's Hospital of Pittsburgh.

There are no exclusion criteria.

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
incidence of acute graft versus host disease (GVHD)	up to 5 years	grades 3-4, chronic extensive GVHD
overall survival after HSCT	up to 5 years	review of the existing medical records to check on the participant's survival status

Secondary Outcome Measures

Name	Time	Method
Describe probability to discontinue systemic immunosuppression medications	by 6, 9, and 12 months post-HSCT	review of the existing medical records to check on the participant's current medications
Describe the tempo of immune reconstitution	over the first year post transplant	review of the various test results in existing medical records to check on the participant's immune system recovery rate
Describe degree of engraftment, based upon chimerism data	up to 5 years	review of chimerism test results in the existing medical records to check on degree of donor engraftment measured by the percentage of donor-derived blood cells in the HSCT recipient
Describe the use of donor leukocyte infusion (DLI)	up to 5 years	review of the existing medical records to check on the participant's need for DLI

Trial Locations

Locations (1)

UPMC Children's Hospital of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States